Rrbp1-flox Mouse

RRBP1, also known as ribosome-binding protein 1 or P180, is a ribosome-binding transmembrane protein of the endoplasmic reticulum. It is involved in multiple biological functions.

In normal physiological conditions, it contributes to processes such as local translation in axons, where it binds to mRNAs enriched for axonal membrane proteins and regulates local translation through its role in axonal ER-ribosome interactions [2]. It also plays a part in the regulation of mitophagy. When there is mitochondrial protein import stress (MPIS), RRBP1 relocates to the mitochondrial vicinity, and together with NLRX1, controls the recruitment and lipidation of LC3, a crucial step in mitophagy [1,8].

In disease-related studies, RRBP1 shows potential oncogenic properties. In upper tract urothelial carcinoma (UTUC), gene body hypomethylation of RRBP1 is associated with its high expression, which is related to carcinogenesis, metastasis, and chemoresistance [3]. In bladder cancer, high RRBP1 expression is associated with tumor stage, lymph node metastasis, and shorter overall survival time, and its knockdown inhibits cell migration and invasion [4]. In oral squamous cell carcinoma, RRBP1 up-regulation is related to cisplatin-resistance, and its inhibition restores cisplatin-mediated cell death [5]. In prostate cancer, METTL3 stabilizes RRBP1 mRNA in an m6A-dependent manner, and RRBP1 exerts an oncogenic role [7]. In epithelial ovarian cancer, high RRBP1 expression is related to FIGO stage, histological grade, histological type, and lymph node metastasis, and is an independent predictor of overall survival and disease-free survival [9]. In prostate cancer, RRBP1 expression is significantly higher compared to non-cancerous tissues and is associated with T stage, lymph node metastasis, PSA, and Gleason score, serving as an independent prognostic factor [10]. In bone metastatic cancer, depletion of RRBP1 enhances the osteoblastic phenotype expression, suggesting its role in the bone microenvironment [6].

In conclusion, RRBP1 has essential functions in normal biological processes like local translation and mitophagy. In disease, especially in multiple types of cancers, it is closely associated with tumor malignancy, metastasis, and chemoresistance. Studies on RRBP1, including those using gene-knockout or conditional-knockout models if applicable in the future, help to understand its role in these biological processes and diseases, potentially providing new targets for cancer treatment.